Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 483, Issue 2, Pages 904-909Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2017.01.032
Keywords
Hepatitis C virus; Polyamines; Spermine; Spermidine; Metabolism
Categories
Funding
- Russian ministry of education and science [14.616.21.0043]
- French National Agency for AIDS and Viral Hepatitis Research [14370]
- Comite de Saone-et-Loire de la Ligue contre le cancer
- Agence Nationale de Recherche
- Region Rhone-Alpes
- DevWeCan French Laboratories of Excellence Network (Labex) [ANR-10-LABX-61]
- OpeRa IHU program [ANR-10-IBHU-004]
- Academy of Finland [266196]
- UEF
- PHC Kolmogorov
- Academy of Finland (AKA) [266196, 266196] Funding Source: Academy of Finland (AKA)
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Chronic infection with hepatitis C virus (HCV) induces liver fibrosis and cancer. In particular metabolic alterations and associated oxidative stress induced by the virus play a key role in disease progression. Albeit the pivotal role of biogenic polyamines spermine and spermidine in the regulation of liver metabolism and function and cellular control of redox homeostasis, their role in the viral life cycle has not been studied so far. Here we show that in cell lines expressing two viral proteins, capsid and the nonstructural protein 5A, expression of the two key enzymes of polyamine biosynthesis and degradation, respectively, ornithine decarboxylase (ODC) and spermidine/spermine-N1-acetyl transferase (SSAT), increases transiently. In addition, both HCV core and NS5A induce sustained expression of spermine oxidase (SMO), an enzyme that catalyzes conversion of spermine into spermidine. Human hepatoma Huh7 cells harboring a full-length HCV replicon exhibited suppressed ODC and SSAT levels and elevated levels of SMO leading to decreased intracellular concentrations of spermine and spermidine. Thus, role of HCV-driven alterations of polyamine metabolism in virus replication and development of HCV-associated liver pathologies should be explored in future. (C) 2017 Elsevier Inc. All rights reserved.
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